Wednesday, October 17, 2012

Pharmacological Starvation: 30% Increased Life Expectancy w/ Still to be Developed FGF21 Analog - The Royal Road To Longevity? Plus: Ground Yourself It's World Nutrition Day!

Do you really think this kid cares whether there is fructose in his/her banana? Think about that before you delve into the next religious discussion about whether or not food a is legit to eat, "not paleo" or "too high in carbs" *thank you*
It's World Food Day and I thought it may be nice to remind everyone about the hilariousness of such "important" first world problems as "eating X bananas a day is bad foryou", the notion of "non paleo" foods and the rest of the vitally important topics the blogosphere is so fond of, these days. Allegedly, neither the bloggers, nor the facebookers or forum posters, who spend so much time and energy debating these and similarly worldshaking issues, will be among the 24,000 human beings who are dieing each and every day from hunger, but maybe one or another of you, of whom I am sure that they don't belong to the group of real notorious nitpickers, will have a similar "grounding experience", from just being reminded of this figure, as me, when I heard it on the radio earlier this morning.

Don't get me wrong, I am not intending to point with a finger at anyone (if anything I would have to start with pointing at myself), but if one or another of you would pause for a second or two and have a similar "grounding experience" as I had, I would be happy.

From real starvation to starvation science
 
Although this prelude appears to segue quite nicely into today's science post, I am not sure if that's even a good thing... be that as it may, after listening to the news on the radio I was quite annoyed, when I read about a recent study by Zhang, Kliewer et al. on the wonderful effects of the "starvation hormone" FGF21 (fibroblast growth factor 21; the effects were observed in mutants who overexpressed FGF21, by the way) on yet another of those awful copy & paste items on Science Daily that are 99% hype and 1% science (in the scientists' defense it must be said that I am well aware of the fact that our, i.e. university or institutionalist, press offices are writing this stuff together in this way on purpose and are not really interested in the actual science background, though). With statements such as "[the mice] got the benefits of dieting without having to limit their food intake" (UT Southwestern Medical Center. 2012) the "article" tailors perfectly to the demands of the glutenous Westerner who applies his "the more the better" principle to all areas of his super sized life that people will probably already be emailing Dr. Kliever about the release date of the drug he surely must be working on.

And in fact, the actual results of the study (Zhang. 2012), the press release specifies by quoting Kliever who said "Male mice that overproduced the hormone had about a 30 percent increase in average life span and female mice had about a 40 percent increase in average life span" sound intriguing. After all this would mean that you would have a realistic chance of making it to the magic 100, when you would otherwise have died at the age of 77.

Starvation, real or hormonal is not the way to healthy longevity!

Nonetheless, the price you would have to pay to "starve yourself into this biblical age" - pharmacologically, of course since (a) otherwise no one could make money on it and (b) no one would want to do it - is high. And I am not sure any of you is willing to pay it.
Figure 1: What do you call it, when mice simply won't grow and end up as a small copy of their normal counterparts with identical body composition, but virtually no bone mass? Right! That's failure to thrive. Now, what do you call the same phenomenon, if the poor critters live 30% longer? Yeah, righ! That's a scientific break through!
I guess you could say you can cope with being a shrimpy weed (or a tiny version of yourself, which is actually what what you would be if you had half your current weight and the same totally average body composition; see figure 1), if that means that you can see your grand grand children rise, but your chances that this is going to happen outside of a wheelchair are not particularly high for men and the chance of seeing them at all is non-existent for women.

The combination of low bone mass and infertility should actually ring a bell with everyone who has been following the Athlete's Triad Series.
Why is that? Well, next to being a pathetic weed, your bone mass and density would be so low that the chances of literally breaking apart are probably way higher than the already low chance that any of these results do even translate to human beings.

And while men who like to gamble may want to make this bet with the pharmaceutical devil, the antifertility effect of FGF21 would not allow any women making the same bet to even have children. Which does obviously not make it very likely that they will ever get to see the children of their grand children - regardless of whether they become 200 years old, by the way.

I am therefore not so sure whether the mere fact that the FGF21 mutants' mobility was not effected is evidence enough of "living a nice, long life", as Kliewer is pointing out (UT Southwestern Medical Center. 2012).

There is no way this drug will be gluttony and thus "Western lifestyle" compatible 

Figure 2: Don't be fooled! The small "g/g body weight" makes all the difference! If you weigh half of a normal human being thanks to whatever patented FGF21 derivate you take, you better make sure you eat like half a human being, as well, if you don't want to shorten your life by 30%, instead of prolonging it!
And as far as the implicit promise of being able to eat "as much as you want" goes, it may be correct that "there were no differences in food intake, physical activity, oxygen consumption or respiratory exchange ratio" (see figure 2) but if you scrutinize the caption of the Y-axis you'll see the bad, bad letters "g/g body weight". And this label means nothing else than that whoever has written the press release has been trying to fool you, when he or she wrote
"The mice that overproduced FGF21 in this latest study were lean throughout their lives and remained lean even while eating slightly more than the wild-type mice, the researchers said." (UT Southwestern Medical Center. 2012)
The truth is, they ate almost half as much as the normal animals, so where on earth was this not a starvation diet? I mean, all of you who have read parts (better the whole) SuppVersity Athlete's Triad Series will be well aware that bone loss and infertility are hallmark features of in this case exercise induced "starvation".

And let's be honest, unless Mc Donalds is going to produce XXS Menues for people on FGF21, I can guarantee you that the only effect any future drug analog of this hormone is going to have is to make people's lives even more miserable than they already are... longevity? No way! After all, this is not going to correct the dietary induced failure of our natural satiety response that constantly drives us to overeat on all those things the people who are now probably lining up in front of Mr. Kliewer's office to be part of the earliest trial are not willing to give up, although they know that they are thus easily reducing their maximal life-expectancy by 30%!

The unsexy, since inconvenient truth is missing from the mainstream science breakdown

In view of the fact that neither the press guy (or girl) nor the scientists appear to have a wested interest to tell you that FGF21 activity is "paradoxically elevated in obese conditions" (Fletcher. 2012) and that something as awfully inconvenient (and moreover non-patentable!) as exercise is the best way to normalize not only the skewed FGF21 levels, but also to increase the expression of the "longevity factor" clotho (30-50% in a classic rodent model; cf. Fletcher. 2012), I consider it my duty to let you know that you neither have to resort to the exogenous provision of drugs, nor starve yourself and can still be sure to benefit from the effects of FGF21: Either by its modulation via exercise if you are obese as the aforementioned rodents or, more importantly, by its upregulation in normal weight individuals, like the 60 sedentary young women Cuevas-Ramos et al. put on a two week exercise regimen earlier this year, only to find that their
"[s]erum FGF21 levels significantly increased after two weeks of physical activity [and that this 66%! increment in FGF 21] correlated positively with clinical parameters related to the adrenergic and lipolytic response to exercise." (Cuevas-Ramos. 2012)
Now, I don't know about you, but I, for my part, would probably risk to make a bet with the devil (pharmacological or not) that anyone who is willing and able to appropriately fuel his workouts, get his share of anabolic and restorative sleep and refrain from overtraining, will get all the benefits, the press release aptly ties solely to the unquestionable pharmacological "separation of the hormone’s life span-extending effects", Kliever is cited for in the last paragraph of the copy & paste job, without any of the downsides.

The SuppVersity Approach to Longevity is therefore simple, cheap and 100% healthy: Work out, eat healthy and get your daily dose of SuppVersity news to know how you can optimize your training, nutrition and supplementation regimen ;-)

References:
  • Cuevas-Ramos D, Almeda-Valdés P, Meza-Arana CE, Brito-Córdova G, Gómez-Pérez FJ, Mehta R, Oseguera-Moguel J, Aguilar-Salinas CA. Exercise increases serum fibroblast growth factor 21 (FGF21) levels. PLoS One. 2012;7(5):e38022.
  • Fletcher JA, Meers GM, Laughlin MH, Ibdah JA, Thyfault JP, Rector RS. Modulating fibroblast growth factor 21 in hyperphagic OLETF rats with daily exercise and caloric restriction. Appl Physiol Nutr Metab.
  • UT Southwestern Medical Center. Newsroom. Starvation hormone markedly extends mouse life span, without need for calorie restriction. Oct 16, 2012. < http://www.utsouthwestern.edu/newsroom/news-releases/year-2012/october/starvation-hormone-mangelsdorf-kliewer.html > retrieved Oct 16, 2012.
  • Zhang Y, Xie Y, Berglund ED, Coate KC, He TT, Katafuchi T, Xiao G, Potthoff MJ, Wei W, Wan Y, Yu RT, Evans RM, Kliewer SA, Mangelsdorf DJ. The starvation hormone, fibroblast growth factor-21, extends lifespan in mice. elife. 2012;1:e00065. doi: 10.7554/eLife.00065.